The problem: Patients receiving therapeutic radiation are at risk of adverse toxic effects. These adverse events are usually unpredictable and may result in severe morbidity or mortality. Example: A third or more of patients receiving chest radiation for cancers of lung may develop life-threatening acute radiation pneumonitis. The clinical need: There is a clinical need for an objective test to estimate the biologic response to therapeutic radiation. Such a test would identify patients at increased risk of an adverse event early in the course of treatment, and enable the treating physician to reduce the radiation dosage. Breath testing - a new solution to the problem: Breath testing could provide a rational tool to estimate the biologic response to radiation therapy, because radiation causes oxidative stress in tissues, resulting in the excretion of volatile organic compounds (VOCs) in the breath. Breath biomarkers have accurately identified exposure to radiation in previous animal and human studies. BreathX - an advanced new breath testing system: Breath X is a rapid, cost-effective and userfriendly system for detection of volatile biomarkers in breath. Breath X employs ultra-clean balloons for collection of breath samples that are analyzed with a comparatively inexpensive tabletop gas chromatograph. BreathX offers a new opportunity to rapidly test for biological response to radiation and potentially identify patients at risk of adverse toxic effects. Proposed research: We will validate the BreathX breath test as a new tool to estimate biological response to radiation. The short-term objective (Phase 1) is to demonstrate proof of principle in animals and in in-vitro studies. The long-term objective (Phase 2) is to validate the test in patients receiving therapeutic radiation in order to estimate their biologic response to radiation and to identify those at increased risk of an adverse event. Potential benefits of the research: A BreathX breath test during the earliest stage of therapeutic radiation could identify patients at increased risk of an adverse response. By alerting the physician to adopt a reduced dosage plan, a BreathX breath test could benefit patients by reducing their risk of mortality and morbidity, and also benefit the healthcare system by reducing the costs that would have resulted from adverse responses.